Na+/H+ exchangers in the human eccrine sweat duct.

Using an anti-NHE1 antibody, we demonstrate the presence of a Na+/H+ exchanger of isoform 1 (NHE1) in the human eccrine sweat duct. A strong staining was observed at the basolateral membrane of the outer cell layer (NHE1basal), at the junction between inner and outer cells layers (NHE1inter), and along the lateral membranes (NHE1later) of all cells of the duct. At the luminal membrane, no staining was demonstrated either for NHE1 or NHE3. To investigate Na+/H+ mediated proton transport, straight sweat duct portions were isolated and perfused in vitro under HCO3-free conditions. In the presence of basolateral 5-ethyl-N-isopropyl amiloride (EIPA), an acidification of 0.29 +/- 0.03 pH units was observed, whereas no effect was observed with luminal EIPA. Bath sodium removal generated a stronger acidification (0.41 +/- 0.09 pH units). Removal of luminal sodium (in the absence or presence of basolateral EIPA), or low luminal chloride, led to an alkalinization, presumably due to a decrease in intracellular sodium, strongly suggesting functional activity of NHE1inter. We therefore conclude that in the sweat duct, NHE1 plays a major role in intracellular pH regulation.

Effect of antiperspirants on whole body sweat rate and thermoregulation.

It is well established that the evaporation of sweat from the human body surface is the main mechanism by which heat balance is maintained following a rise in body core temperature. Since the introduction of the first brand name antiperspirant in the United States during the early 1900s, antiperspirant products designed to control underarm wetness have grown to represent one of the largest cosmetic categories in most global markets. However, although axillary sweating only constitutes less than 1% of whole body sweat rate, consumers, particularly in hot countries, have begun to articulate the concern that antiperspirants may interfere with the body's natural cooling process. To investigate this, we undertook carefully designed experiments that measured the effects of axillary antiperspirant application on whole body sweat rate and body core temperature, following a regimen of exercise-induced heat stress in a hot environment in human volunteers. Our data show clearly that although antiperspirant prevents sweat production in the axillary area, this does not impact the ability of the body to thermoregulate following a rise in body core temperature. Thus, recent consumer questioning over this aspect of antiperspirant use appears to be unwarranted.

V-type H+-ATPase in the human eccrine sweat duct: immunolocalization and functional demonstration.

We investigated for the presence of a vacuolar-type H+-ATPase (V-ATPase) in the human eccrine sweat duct (SD). With the use of immunocytochemistry, an anti-V- ATPase antibody showed a strong staining at the apical membrane and a weaker one in the cytoplasm. Cold preservation followed by rewarming did not alter this staining pattern. With the use of the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein on isolated and perfused straight SD under HCO-free conditions and in the absence of Na+, proton extrusion was determined from the recovery rate of intracellular pH (dpH(i)/dt) following an acid load. Oligomycin (25 microM), an inhibitor of F-type ATPases, decreased dpH(i)/dt by 88 +/- 6%, suggesting a role for an ATP-dependent process involved in pH(i) recovery. Moreover, dpH(i)/dt was inhibited at 95 +/- 3% by 100 nM luminal concanamycin A, a specific inhibitor of V-ATPases, whereas 10 microM bafilomycin A1, another specific inhibitor of V-ATPases, was required to decrease dpH(i)/dt by 73%. These results strongly suggest that a V-ATPase is involved in proton secretion in the human eccrine SD.

Combined spinal epidural anaesthesia for caesarean section: a randomised comparison of Oxford, lateral and sitting positions.

Maternal position during induction of intrathecal anaesthesia for caesarean section influences block height and haemodynamic stability. In a randomised study of 90 women presenting for elective caesarean section using combined spinal-epidural anaesthesia, three positions were compared--the Oxford position (group O), the right lateral to supine wedged (group R) and the sitting to supine wedged (group S). Hyperbaric bupivacaine 12.5 mg with fentanyl 12.5 microg was injected intrathecally using a needle-through-needle CSE technique. Intravenous ephedrine 6 mg was given every minute that systolic blood pressure fell below 80% of baseline. Time required for block height to reach T5 as assessed by light touch, was similar in the three groups. There were no significant differences in blood pressure although ephedrine requirements were less in group R. There were no significant differences in the incidence of maternal nausea and vomiting or in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis. Although the study failed to show any significant differences in block height between the groups, no women in group O had a block above T2 compared with three in group R and three in group S.

Erroneous gender differences in axillary skin surface/sweat pH.

Assessing accurately the pH of axillary eccrine sweat is of vital importance in the antiperspirant industry. Eccrine sweat pH is a critical parameter in determining the effectiveness of antiperspirants; antiperspirant salts dissolve in sweat and diffuse into the sweat glands, where the resultant acidic solution hydrolyses in more alkaline sweat forming an amorphous metal hydroxide gel, thereby restricting the flow of eccrine sweat. Comparison of the skin surface and sweat pH of males and females reported in the literature shows that, although consistent male/female differences have been observed on the forearm, determination of significant gender-based pH differences across other sites are less conclusive. Studies on the back and infra-mammary regions exhibited significant gender differences in skin surface pH, whereas those on the forehead, cheek, neck and inguinal area showed no such difference. With regard to the axilla specifically, four studies have been reported, three showing no significant difference in axillary skin surface pH and one indicating that females have an eccrine sweat pH of 7 and males have a sweat pH of 5.6. This paper describes a series of carefully controlled studies aimed at assessing potential gender differences in eccrine sweat and skin surface pH following exposure to a variety of temperature, humidity and time conditions. The results highlight the importance of controlling precisely the time of investigation, site of measurement and, most importantly, the necessity to pre-equilibrate samples in 40 mmHg carbon dioxide (equivalent to arterial CO(2) tension (pCO2)) before determining sweat pH. When these parameters are controlled no gender differences in axillary sweat or skin surface pH are observed. Large differences in eccrine sweat and skin surface pH are found, however, between the vault (hairy region) and fossa (non-hairy region) of the axilla.

Circadian rhythms in axillary skin surface pH.

Sweat and skin surface pH are critical parameters in determining the performance of antiperspirants. The mechanism of action, the so-called 'plug theory' first proposed by Reller and Luedders, involves the expression of eccrine sweat onto the surface of the skin into which the solid antiperspirant salts, typically an aluminium chlorohydrate or zirconium aluminium glycine, dissolve. The resultant acidic 'solution' then diffuses with time into the sweat glands, where it hydrolyses in more alkaline sweat and forms an amorphous metal hydroxide agglomerate that physically plugs the ducts some 20-100 mum into the glands. It is therefore important to understand whether diurnal variations in skin surface pH exist in the axilla, as these may influence strongly the time of day at which antiperspirant should be applied in order to yield maximal protection. Clinical studies demonstrate a significant fall in axillary skin surface pH between the morning (pH = 5.87 +/- 0.23) and the evening (pH = 5.49 +/- 0.23). This diurnal variation in skin surface pH suggests that antiperspirant efficacy will be optimal when products are applied in the morning. In addition, the data suggest a circadian rhythm in axillary skin barrier function, indicating that chronopharmacology, the timing of administration of medication, could be used to optimize treatment of axillary hyperhidrotics using topical administration of anticholinergic drugs.

A comparison of bupivacaine-fentanyl-morphine with bupivacaine-fentanyl-diamorphine for caesarean section under spinal anaesthesia.

In a randomised double-blind trial, postoperative analgesia and side effects of intrathecal morphine 0.1 mg and intrathecal diamorphine 0.25 mg were compared. Sixty women were randomised to receive intrathecal injection of 12.5 mg hyperbaric bupivacaine and 12.5 microg fentanyl with either morphine 0.1 mg (group M), or diamorphine 0.25 mg (group D). All women received 100 mg diclofenac rectally at the end of surgery and were given intravenous morphine via a patient controlled analgesia (PCA) system. Pain, PCA morphine usage and side effects were assessed at 2, 4, 8 and 24 h after spinal anaesthesia. The two groups were comparable for quality of intraoperative analgesia. There were no significant differences between the groups in time to first PCA demand, morphine consumption or oral analgesic use in each time period. Significantly more patients in group M were nauseated at 4 h whilst at 24 h nausea was significantly worse in group D. There was no significant difference between the groups in the number of women vomiting in the 24-h period. The two groups were comparable for pruritus and drowsiness. We conclude that 0.25 mg subarachnoid diamorphine is a suitable alternative to 0.1 mg morphine for post caesarean section analgesia.

Vacuolar-type H+ -ATPase distribution in unstimulated and acetylcholine-activated isolated human eccrine sweat glands.

The presence and cellular distribution of subunits of the V1 sector of the vacuolar-type H+ -ATPase (V-ATPase) was investigated in isolated human eccrine sweat glands. In every instance, V-ATPase was located in the cytoplasm and apical membranes of the luminal cells of the reabsorptive duct segment. In the secretory coil, both diffuse and perinuclear staining was demonstrated in the secretory cells, with additional expression at the apical and basolateral membranes and on the intercellular canaliculi. There was no detectable difference in V-ATPase expression as a result of prior application of 100 microM acetylcholine.

Selective changes in GABAergic transmission in substantia nigra and superior colliculus caused by ethanol and ethanol withdrawal.

One of ethanol's actions after acute exposure is anticonvulsant activity whereas withdrawal from chronic ethanol exposure increases convulsant activity. An increase in neuronal transmission in the GABAergic pathways from striatum to the substantia nigra (SN) and a decrease in GABAergic transmission from SN to superior colliculus (SC) both appear to play a major role in inhibiting seizure propagation. If this is the case, then the changes in seizure sensitivity caused by ethanol may be expected to affect GABAergic transmission in opposite ways in SN and SC. We measured the effects of in vitro ethanol on pre- and postsynaptic indices of GABA transmission using SN and SC tissue from both ethanol-naive rats and rats given ethanol in their drinking water for 24 days and then withdrawn for 24 hr, a treatment that decreases seizure latency. While ethanol inhibited 3H-GABA release from slices of SC at low concentrations (20-100 nM), much higher concentrations were required to inhibit release from SN (100-500 mM). In fact, release from SN was increased by low concentrations of ethanol. Ethanol in vitro (20-1000 mM) also inhibited specific binding of 35S-TBPS to the GABAA receptor but this effect was similar in both potency and efficacy in SC and SN. Next, the in vitro effects of ethanol were measured in rats that had consumed an average of 9.8 g ethanol/kg body weight/day and were then withdrawn for 24 hr. Ethanol inhibition of 3H-GABA release from SC was significantly less in ethanol-treated rats compared to controls whereas the inhibitory effect of ethanol was increased in SN from ethanol-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)